This proposal is concerned with the structural elucidation of glycosaminoglycans (mucopolysaccharides), and with chemical transformations of simple, readily available polysaccharides into synthetic glycosaminoglycans of potential utility as inexpensive blood anticoagulants, antilipemic, and cancer-chemotherapeutic agents. Especial emphasis will be placed upon synthesizing polymers having the structure of heparin, a complex, sulfated glycosaminoglycan, and in determining fine details of its structure. Heparin, used widely in therapy for cardiovascular conditions arising from formation of blood surface-coating for artificial replacements in the circulatory system, is also of interest as a nonthrombogenic surface-coating for artificial replacements in the circulatory system, and as an antilipemic agent for lowering blood-lipid levels. Structural details are to be elucidated by full chemical characterization of fragments obtained from heparin that has been isolated from mammalian tissue in unmodified form. Newer techniques for structure determination, notably chemical-ionization mass spectrometry, will be used to devise a rapid, small-scale procedure for determining the linkage sequence in segments of the glycosaminoglycan chain. Characterization of fragments will define the anomeric nature of the interglycosidic linkages, the linkages between heparin and protein in the source tissue, the placement of all sulfate groups, and the ratio of uronic acid residues in the polymer. The structural methodology thus devised should be of general value for the chemical delineation of tissue changes associated with vascular pathological conditions and aging. Aminated polysaccharides, intermediate in the syntheses will be evaluated as aggregants and growth inhibitors acting as specific cytotoxic agents for cancer cells. These polycationic products will be further modified to prepare a range of water-soluble cationic polymers for evaluation as cancer-specific cytotoxins. BIBLIOGRAPHIC REFERENCES: 2,5-Anhydro-D-mannitol, Via Nitrous Acid Deamination of 2-Amino-d-deoxy-D-glucopyranose Hydrochloride to 2,5-Anhydro-D-mannose, D. Horton and Kerstin D. Philips, Methods Carbohydr. Chem., 7, 68-70 (1976).